Mechanical Signals in Vessel Development

船舶开发中的机械信号

基本信息

批准号：
8034247
负责人：
Jessica Wagenseil
金额：
$ 24.9万
依托单位：
SAINT LOUIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8034247
关键词：
A Mouse Adult Affect Animals Architecture Biomechanics Biomedical Engineering Blood Blood Pressure Blood Vessels Blood flow Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cell physiology Cellular biology Characteristics Collagen Communication Data Development Disease Educational process of instructing Elastin Extracellular Matrix Proteins Gene Expression Growth Human Hypertension Knowledge Laboratories Life Longevity Measures Mechanical Stress Mechanics Mentorship Modeling Mus Patients Play Principal Investigator Process Proteins Radial Recruitment Activity Research Research Training Role Saints Signal Transduction Smooth Muscle Myocytes Staging Stimulus Stress Structure Supravalvular aortic stenosis System Testing Training Universities Washington base career hemodynamics mathematical model mature animal mechanical behavior meetings mouse model predictive modeling pressure professor programs skills tool treatment strategy

项目摘要

This proposal outlines a three year program of research and training td establish the principal investigator (PI) as a biomedical engineering professor studying develqpmeiital cardiovascular mechanics. A postdoctoi-al year has been completed In Dr. Robert Mecham's laboratory at Washington University, where the PI expanded her knowledge of cell biology and physiology and practiced communication and management skills. The PI has accepted a tenure-track assistant professorship at Saint Louis University and plans to continue'her previous research. She will establish her independence by combining the cell biology and physiology with her expertise in biomechanics and mechanical modeling. Career training w/lir include teaching, mentorship by established professors and exposure at national meetings: During cardiovascular development, blood pressure and flow increase and smooth muscle cells produce extracellular matrix proteins, such as collagen and elastin. that define the mechanical behavior of the vessel wall. A mouse .model o( supravalvular aortic stenosis, an elastin-associated disease in humans, showed that elastin haploinsufficiency (eln+/-) results in altered vessel wall structure, decreased compliance and Increased blood pressure. Despite these features. eInW- mice live a normal life span, suggesting that they adjust to reduced elastin amounts and the resulting changes Iri rriechanicat stimuli. The hypothesis of this proposal is that developing vessels remodel to optimize mechanical stresses in the wall and that these stresses, provide a key signal for cellular differentiation. This remodeling will be described and predicted by a mathematical model in which pertiirbations cause grovi/th of various components, returning the stresses near homeostatic values. Because of the unique developmental remodeling in the eln+/-.cardiovascular system, these mice provide an Ideal tool to investigate the hypothesis and validate the mechanical model. The specific aims are: 1) To detennine hemodynamic, mechanical and geometric parameters In developing vessels. 2) To determine how changes in elastin amount alter mechanical sigriats in developing vessels. 3) To develop a constrained mixture model lo predict the growth of developing vessels.

该提案概述了一项为期三年的研究和培训计划，旨在确定主要负责人研究员（PI），作为生物医学工程教授，研究开发心血管力学。华盛顿大学罗伯特·梅查姆博士的实验室已经完成了一年的博士后工作， PI 在这里扩展了她的细胞生物学和生理学知识，并练习了沟通和交流管理技能。 PI 已接受圣路易斯大学终身教授助理教授职位并计划继续她之前的研究。她将通过结合细胞来建立她的独立性生物学和生理学以及生物力学和机械建模方面的专业知识。职业培训w/lir 包括教学、知名教授的指导以及参加全国会议：在心血管发育过程中，血压和血流量增加，平滑肌细胞产生细胞外基质蛋白，例如胶原蛋白和弹性蛋白。定义机械行为血管壁。瓣膜上主动脉狭窄（一种人类弹性蛋白相关疾病）的小鼠模型表明，弹性蛋白单倍体不足（eln+/-）会导致血管壁结构改变、顺应性降低和血压升高。尽管有这些特征。eInW-小鼠的生活正常的寿命，表明它们会适应弹性蛋白数量的减少以及由此产生的变化 Iri rriechanicat 刺激该提议的假设是开发血管重塑以优化机械应力。这些压力为细胞分化提供了关键信号，该模型将通过数学模型来描述和预测，其中扰动会导致各种组件的生长，从而使压力返回到接近稳态值。这些小鼠在 eln+/-.心血管系统中进行重塑，为研究假设和验证机械模型提供了理想的工具。具体目标是： 1) 确定开发血管中的血流动力学、机械和几何参数。 2) 确定弹性蛋白量的变化如何改变发育中血管的机械特征。 3) 开发一个约束混合模型来预测发育中血管的生长。